Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53-or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53-or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53-and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53-and VEGF-negative tumors, while 52.2% of patients with both-positive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors. Our findings suggest the presence of a p53-VEGF pathway regulating tumor angiogenesis in human colorectal carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.

RESULTS.A complete response was observed in 2 cases and a partial response in 1 First Department of Surgery, Osaka City Uni-11 cases, for an overall response rate of 50%. Patients with good performance versity Medical School, Osaka, Japan.status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferenti-2 Institute for Pathogenic Biochemistry in Medicine, Taiho Pharmaceutical Company, Tokyo, ated histologic type (28.6% and 35.3%, respectively), although there were no sigJapan.nificant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption.CONCLUSIONS. FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity.

Tumor‐resident memory T (T RM ) cells in primary tumors are reportedly associated with a favorable prognosis in several malignancies. However, the behaviors and functions of T RM cells in regional lymph nodes (LNs) of esophageal cancer remain poorly understood. The aim of this study was to elucidate the effects of T RM cells in regional LNs of esophageal cancer on clinicopathological findings and prognosis. Specimens of esophageal cancer and primary metastatic LNs (recurrent nerve LNs) were obtained from 84 patients who underwent radical esophagectomy between 2011 and 2017. We performed immunohistochemistry to enumerate and analyze T RM cells, and used flow cytometry to investigate the function of T RM cells. T RM cells were observed in both metastatic LNs and primary tumors. T RM cell‐rich specimens exhibited reduced lymphatic invasion and LN metastasis and prolonged survival compared with T RM cell‐poor specimens. T RM cells in metastatic LNs were more significantly associated with enhanced survival than T RM cells in primary tumors. T RM cells expressed high levels of granzyme B as a cytotoxicity marker. Our results suggested that high T RM cell infiltration in metastatic LNs improves survival even though LN metastasis is commonly associated with poor prognosis. T RM cells possibly contribute to antitumor immunity in regional LNs.